Differential effects of unaggregated and aggregated amyloid β protein (1–40) on K[sup +] channel currents in primary cultures of rat cerebellar granule and cortical neurones.

Autor: Ramsden, M., Plant, L.D., Webster, N.J., Vaughan, P.F.T., Henderson, Z., Pearson, H.A.
Předmět:
Zdroj: Journal of Neurochemistry; 11/1/2001, Vol. 79 Issue 3, p699-712, 14p, 2 Black and White Photographs, 20 Graphs
Abstrakt: The effects of amyloid β protein on voltage-gated K[sup +] channel currents were studied using the whole-cell patch-clamp technique. The 1–40 amino acid form of amyloid β protein was applied to primary cultures of rat cerebellar granule and cortical neurones for 24 h. Both the unaggregated and aggregated forms of the peptide, which have differing biological activities, were used. In cerebellar granule neurones, 24-h pre-incubation with 1 µm unaggregated amyloid β protein resulted in a 60% increase in the ‘A’-type component of K[sup +] current. Increased delayed rectifier activity was Cd[sup 2+]-sensitive and was presumed to be secondary to an increase in voltage-gated Ca[sup 2+] channel current activity. Unaggregated amyloid β protein had no effect on any component of the K[sup +] channel current in cortical neurones. One micromolar of aggregated amyloid β protein had no effect on K[sup +] channel current in either cell type but reduced cell survival within 24 h as measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assays. The unaggregated form of amyloid β protein had no neurotoxic effects when applied to either neurone type for up to 72 h. These data indicate that the unaggregated, non-pathological form of amyloid β protein causes changes in the ion channel function of neurones, possibly reflecting a physiological role for the peptide. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
Externí odkaz: